The present invention provides novel compounds of formula I ##STR2## which are pharmacologically useful as cardiovascular agents. More specifically, the compounds of the present invention promote renal, coronary and peripheral vasodilation by the antagonism of calcium ions at arteriolar vessels. Thus, the compounds of the invention are useful generally as vasodilators, and specifically as calcium ion antagonists, antihypertensive agents, and anti-anginal agents, for example. The present invention also relates to novel pharmaceutical compositions comprising one or more of the active compounds of the invention in combination with suitable pharmaceutical carriers as well as methods of using such compounds and pharmaceutical compositions thereof in the treatment, prevention, or mitigation of cardiovascular diseases or conditions such as arrhythmias, angina-pectoris, hypertension, peripheral vascular disorders, etc. wherein abnormalities in the cellular or vascular handling of calcium ions is a causitive factor.
The compounds of formula I comprise (substituted)N-benzyl-4-(benzhydryl) piperidines wherein the substituents on the benzyl moiety thereof are aralkoxy derivatives in which the aryl moiety thereof may be further substituted.
Belgium Pat. No. 862769 discloses diphenyl methylene piperidine derivatives of the formula: ##STR3## in which A.sup.1 -A.sup.4 are H, halo, halomethyl, alkyl or alkoxy which are indicated to have utility as anti-convulsants and cardiovascular agents. The compounds disclosed in the foregoing Belgium patent are structurally unrelated to the compounds of the present invention by reason of the presence of optionally substituted diphenyl methylene (i.e., C.dbd.) attached to the piperidine ring and by the hydroxy substituent on the benzyl moiety rather than the aralkoxy or substitued aralkoxy moiety in accordance with the compounds of the present invention. The hydroxy derivatives disclosed in the foregoing Belgium patent are prepared by hydrolysis of a benzoate ester protected intermediate; however, only the hydroxy benzyl piperidine final products are associated with the indicated utility of the compounds.
U.S. Pat. No. 4035372 discloses 4[[4-(diphenylmethyl)-1-piperidinyl]methyl] benzenamines of the formula ##STR4## wherein Am represents an amino, alkanoylamino, alkylamino or dialkylamino radical and the vasodilating activity thereof. The compounds disclosed are all amino or substituted amino derivatives and, therefore, lack the aralkoxy moiety characteristic of the compounds of the present invention. U.S. Pat. No. 4356184 discloses 1-piperidinylmethyl benzenamines of the following formula: ##STR5## The foregoing compounds represent tricyclic ylidene piperidine derivatives rather than the diarylmethyl compounds of the present invention. Also, the substituent on the N-benzyl group is dialkyl amino rather than aralkoxy (e.g., benzyloxy). The compounds disclosed in the aforementioned U.S. Pat. No. 4356184 are indicated to be useful as anti-allergic and anti-hypertensive agents.